10 bio265 disease of skin and cns instructor dr di bonaventura

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Microbial disease of the skin and wound Bacteria, viruses, fungi, protozoa, and arthropods are involved in skin disease

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Page 1: 10 bio265 disease of skin and cns instructor dr di bonaventura

Microbial disease of the skin and wound

Bacteria, viruses, fungi, protozoa, and arthropods are involved in skin disease

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Normal microbiota of the skin Staphylococccus

S. epidermidis S. aureus

Micrococcus

Diphtheroids

Corynebacterium xerosis

Propionibacterium acnes

Malassezia furfur (yeast)

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Disease of the skin

Staphylococcus aureus causes a variety of disease

Grapelike arrangement of staphylococci

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Virulence factors include enzymes, structures to evade phagocytosis, and toxins

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Staphylococcal Scalded Skin Syndrome

Certain strains of S. aureus secrete exfoliative toxins (toxemia) that cause dissolution of epidermal desmosomes

Cause staphylococcal scalded skin syndrome (SSSS), in which the epidermis peels off in sheets

Person-to-person spread

The bacterium penetrates cuts and abrasions

Susceptible patients

Infants, elderly, immunosuppressed patients

Fluid in blisters does not contain S. aureus

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Impetigo (Pyoderma)

Contagious skin disease caused by S. aureus or Streptococcus pyogens

Red patches pus filled vesicles (from which bacteria spread – vesicles of impetigo are diagnostic) honey-colored crusts

Epidemics of impetigo in nurseries are of particular concern

Person to person contact or via contaminated fomites

Invade through scratches, abrasions, cold sores

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Necrotizing Fasciitis

Commonly caused by S. pyogenes (“flesh eating strep”), the bacterium digests muscle fascia

Person-to-person contact Bacteria enter through breaks in

the skin Intense pain and swelling at

the site of infection Rapid destruction of tissue

within hours

Removal of necrotic tissue Immediate intravenous broad-

spectrum antimicrobial drugs

About 15% of patients die

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Burn patients and Pseudomonas aeruginosa infection

The surface of almost two-thirds of burn victims develops infection by this opportunistic pathogen

Pyocyanin discoloration indicates massive infection caused by P. aeruginosa

Treatment requires debridement Administration of a combination of antimicrobial drugs

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Rocky Mountain Spotted Fever

Tick

Transmitted by infected tick from salivary glands

Caused by Rickettsia rickettsii (Gram negative, obligate intracellular rod-shaped bacterium) Rickettsia infects cells lining small

blood vessels where it replicates

Infected cells release Rickettsia (Genus: Dermacentor)

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Non-itchy, spotted rash on the trunk and appendages, soles, palms

Can develop into petechiae (subcutaneous hemorrhages)

Rocky Mountain Spotted Fever

Damage to blood vessels

Blood escapes, causing low blood pressure, insufficient oxygen and nutrients to the body’s organs

~ 5% of patients die even with treatment

Life-threatening acute RMSF may involve paralysis and secondary infection by Clostridium perfringens

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Number of cases of Rocky Mountain spotted fever in the U.S., 1999-2009

Prevention involves protection against the tick (especially in spring and summer)

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Gas Gangrene

Clostridium species - C. perfringens

Dead tissue from a traumatic event infected with endospores

Endospores will germinate

Toxins released by cells kill the surrounding tissue - necrosis (muscle and connective tissue), providing anaerobic conditions/nutrients

Blackening of the infected muscle/skin and gas production

Death can follow within a week of infection (Shock/coma)

Removal of dead tissue, antitoxins, antibiotics (and oxygen!)

(~40% mortality rate)

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Cutaneous Anthrax and zoonosis

Antrax has three clinical manifestations Cutaneous Inhalation Gastrointestinal

Bacillus anthracis endospores shed by an infected animal come in contact with wounded skin (i.e., farmers) Painless, swollen, black, crusty ulcers called eschar(s)

Cells in the infected area die

Treated cutaneous antrax is rarely fatal (60 days of antibiotics) Prevention involves control of disease in animals (vaccination)

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Viral diseases

Viral diseases are systemic

Spread by oral/respiratory routes, or contact (person-to-person contact/contaminated fomites)

Manifest signs and symptoms in the skin Smallpox (Variola virus) Herpes viruses (Herpes simplex virus) Papillomavirus (Warts) Chickenpox and shingles (Varicella zoster virus) German measles (Rubella) Red measles (Morbillivirus)

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Poxyviruses (Smallpox)

In 1980 natural smallpox was declared eradicated

Concern about smallpox, It could be reintroduced accidentally from storage or through

bioterrorism Most people would be susceptible to smallpox epidemics

since regular vaccination was discontinued decades ago

Smallpox virus - dsDNA

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Smallpox (Variola virus)

Transmitted by inhalation of virus in

droplets (aerosol) or dried crusts

The person is not contagious during the incubation period (12-14 days)

pox Stages of lesions of poxviral skin infections Also used to describe lesions

of other viral infections

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Smallpox (Variola virus)

Immediate immunization of people exposed to smallpox virus prevents the disease from developing

No treatment exist once smallpox develops High fever Malaise Delirium Prostration

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Herpes simplex viruses (dsDNA)

Human herpes virus HHV-1 and HHV-2

Infection occurs when viruses

invade the mucous membranes of lips, genitalia, broken skin of finger

Viruses may remain latent in nerve cells

Recurrent lesions

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Cold sore (fever blister)

Primary HHV-1 infections typically occur during childhood Most HHV-2 infections are acquired between the age of 15-29 as a

result of sexual activity

The virus can cross the placenta infecting the fetus/more likely that a baby is infected at birth

No cure exist but drugs (acyclovir) can shorten outbreaks

Herpes simplex viruses

Active lesions are a source of infection

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Papillomaviruses (dsDNA) – many different strains

Papillomaviruses cause warts (epithelial growth of the skin or mucous membranes)

Transmitted via direct contact (including sexual intercourse), childbirth, and fomites

Papilloma virus of genital warts has been linked to cervical cancer (vaccine)

Prevention of genital warts is possible by mutual monogamy

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Chickenpox and shingles

Varicella-zoster virus (dsDNA) causes both chickenpox and shingles

Inhalation of virus, infection begins in the respiratory tract, spreads via blood (viremia) to skin

Viruses are shed before/during appearance of signs (droplets-aerosols and lesions)

Characteristic lesions on the

back/trunk, face/neck Macule, papule, vesicle, crust

CDC recommends vaccination

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Chickenpox (Varicella) and shingles

Chickenpox virus can become latent

Stress, aging, immunosuppression can reactivate the virus

Producing a painful skin rash known as shingles or herpes zoster (15-20% of adults)

Chickenpox in adults is more severe, it may require hospitalization A person can acquire chickenpox from a shingles patient

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Rubella - (Also known as German measles) -ssRNA

Mild rash (macula) in children

Infections in adults are more severe (arthritis/encephalitis)

The virus crosses the placenta

Rubella infections of pregnant women during the first months results in birth defects, including deafness, blindness or mental retardation

Live, attenuated vaccine against rubella is part of the MMR

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Measles - (rubeola or red measles) – Morbillivirus - ssRNA

Transmitted by respiratory route

Lesions called Koplik’s spots

on the mucous membrane of the mouth provide a diagnosis of measles

Macopapular skin lesions spread over the body, which gradually turn brown

Live, attenuated vaccine (MMR)

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Complications include SSPE: progressive disease of the central nervous system, which

begins 1-10 years after the initial infection, resulting in death Afflicts less then 7 patients/1 million as a result of childhood

immunization

Measles - (rubeola or red measles) - Morbillivirus

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Superficial Mycoses

Affect outer skin layers, hair shafts Direct contact with hyphae/spores of opportunistic fungi

Black piedra – Piedra hortae

Hyphae and spores on hair shafts

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Cutaneous mycoses

Cutaneous infections caused by fungi that grow in the skin Keratin in dead layers of skin, nails, hair is used as a nutrient Rarely become systemic

Athlete’s foot

Tineas (ring worm) Pityriasis versicolor caused by Malassezia furfur, interference with melanin production

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Oral Candidiasis

Factors include: antibiotic therapy, an immunocompromised condition (AIDS), diabetic patients ….

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Caused by Sporotrix schenckii introduced into the skin by thorn pricks or wood splinters (gardeners, farmers, and artisans)

Enters lymphatic system near the site of a primary lesion, it remains in subcutaneous tissues and it does not enter the blood

Topical applications of potassium iodide for months

Lymphocutaneous sporotrichosis

Sporotrichosis, subcutaneous mycoses

Diagnosis Patient’s history Clinical signs Dimorphic nature

of Sporotrix

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Transmitted via prolonged bodily contact or by sharing clothing ….

Sexual transmission is common

Scabies is caused by a mite called Sarcoptes scabiei

Epidemics: people in crowded conditions such as hospitals, nursing homes, prisons

Treatment: mite-killing lotions, cleaning of contaminated items (hot water and hot dryers )

Prevented only by good personal hygiene!!

Intense itching and rash

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Disease of the nervous system

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The CNS is an axenic environment, it has no normal microbiota

Pathogens can gain access to the nervous system Breaks in the bones/meninges Medical procedures (spinal taps) Penetration of the blood-brain barrier leading to

meningitis

Pathogens Can infect cells of the nervous system Release toxins that affect neurons

Nervous system

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Diseases of the nervous system

Bacterial diseases Bacterial meningitis Neurological diseases caused by bacterial toxins

(botulism and tetanus)

Viral diseases Viral meningitis (enteroviruses) Poliomyelitis Rabies Arboviral encephalitis

Fungal disease (yeast)

Cryptococcosis (cryptococcal meningitis)

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Respiratory droplets from infected individuals

Streptococcus pneumoniae pneumococcal meningitis

Neisseria meningitidis meningococcal meningitis

Haemophilus influenzae, type b

Newborns-passage through an infected birth canal

Streptococcus agalactiae

Contaminated food (unpasteurized milk, cheese, raw vegetables or meat) – Transfer to fetuses

Listeria monocytogenes listeriosis

Bacterial Meningitis

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Bacterial Meningitis

Bacteria spread to the meninges via blood (bacteremia)

Bacterial meningitis is characterized by High fever and inflammation of the meninges (cranial/spinal) High number of white blood cells in the CSF Severe headache, nausea/vomiting, pain Drowsiness, confusion

If the brain becomes infected (encephalitis), it can lead to deafness,

blindness, coma or death

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Bacterial Meningitis

Rapid treatment reduces mortality below ~ 15% of cases

CDC recommends vaccination of children against H. influenzae type b, S. pneumoniae, N. meningitidis

Diagnosis involves detection of pathogens in CSF (spinal tap) – High number of leukocytes

Treatment: Intravenous administration of antibiotics

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Viral Meningitis

Viral meningitis (aseptic meningitis) is the most common form of meningitis

Mostly caused by enteroviruses (RNA viruses - cytolytic)

Spread via the bloodstream (viremia) to the meninges Coxsakie A virus Coxsakie B virus Echovirus

Transmission: Fecal contamination of food, water, or hands

(intestinal tract)/Respiratory droplets (lungs) 1/1000 develop viral meningitis

Diagnosis: Signs/symptoms characteristic of meningitis but absence of bacteria in CSF - No specific treatment exist for viral meningitis

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Cryptococcosis affects healthy people and immunocompromised hosts (AIDS patients)

Signs and symptoms common to bacterial meningitis - with a high mortality rate

Cryptococcus neoformans is an encapsulated yeast

Transmitted by inhalation of dried, contaminated droppings (pigeon/chicken)

Diagnosis/treatment involve detection of antigens in CSF and serum/Antifungal drugs

Cryptococcal meninigitis

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Arboviral (Arthropod-born viruses) encephalitis

Transmission of six encephalitis arboviruses

Zoonotic diseases, typically affect birds, horses, rodents

Seasonal incidence related to the mosquitos

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Arboviral (Arthropod-born viruses) encephalitis

WEE-Western equine encephalitis EEE-Eastern equine encephalitis VEE-Venezuelan WNV-West Nile virus St. Louis encephalitis California encephalitis

Diagnosis involves detection of arboviral antigens in the CSF

Signs and symptoms are similar to those of bacterial meningitis

Treatment No specific treatment exist for

arboviral encephalitis but supportive care

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Human West Nile virus encephalitis in the US Can be transmitted between people (blood transfusion and

transplanted organs) Treatment is supportive/No human vaccines approved Limiting contact with mosquito (many different species!!)

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Neurological diseases caused by bacterial toxins

Botulism is caused by Clostridium botulinum

Foodborne botulism (intoxication) Ingestion of botulism toxin in contaminated food

Wound botulism Growth of the bacterium in dead tissue following introduction of

endospores into wounds

Death: 10% of hospitalized patients

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Neurological diseases caused by bacterial toxins

The neurotoxins prevents muscular contraction (skeletal muscle cells), leading to flaccid paralysis

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Neurological diseases caused by bacterial toxins

Infant botulism (usually infants under 6/12 months of age) - most common cause in US

Treatment of botulism includes: administration of immunoglobulins that neutralize the toxin (BIG-IV), washing of intestinal tract to remove Clostridium, antimicrobial drugs to kill the bacterium

Death rate: less than 1% of hospitalized children

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Neurological diseases caused by bacterial toxins

Tetanus is caused by Clostridium tetani

Endospores enter through breaks in the skin - cuts or punctures

Cells release a toxin called tetanospasmin

Axonal transport carries the toxin to the CNS

Initial diagnostic sign is the tightening of the jaw and neck muscles Progression involves continuous muscle contraction Contraction of the diaphragm leads to final inhalation

“Lollipop” endospores

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Tetanus is caused by Clostridium tetani

Treatment Cleansing of wounds to

remove spores Passive immunotherapy

with HTIG Active immunization with

tetanus toxoid (DTaP vaccine)

Antibiotics

Widespread immunization has led to a decline in tetanus incidence in US

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Poliomyelitis is caused by an enterovirus called Poliovirus

Most often transmitted by drinking contaminated water

Poliovirus travels to infect neurons of the CNS

Asymptomatic infections – almost 90% of cases

Minor polio – nonspecific symptoms

Nonparalytic polio – muscle spasms and back pain

Bulbar poliomyelitis A form of paralytic polio The brain stem is infected Paralysis of respiratory

muscles or of muscles in the limbs

Complete recovery or paralysis that is lifelong

“Iron lungs” – before 1955

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Viral disease of the nervous system - Poliomyelitis

The disease has spread in recent years beyond the borders of endemic Countries (India, Nigeria)

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Viral disease of the nervous system – Rabies (ssRNA)

Rabies is a zoonosis, transmitted to human via a bite/breaks in the skin or mucous membranes - viruses are secreted in the saliva

Reservoirs include dogs and cats, foxes, skunks, raccoons, bats

Replicates in skeletal muscle cells, travels to the CNS: function of the brain/spinal cord degenerates

Neurological manifestations characteristic of rabies include Hydrophobia Hallucinations Paralysis (respiratory paralysis

is associated with death)

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Viral disease of the nervous system – Rabies

Postmortem laboratory tests include identification of aggregates of rabies viruses in cells of the cerebellum

Postexposure prophylaxis (PEP)/Treatment: immediate cleansing of the wound, passive immunization, and active immunization before onset of clinical symptoms

Control involves immunization of people who regularly come in contact with wild animals